The Argentine - winner of the US Open in 2010 - was toppled by the Frenchman in Melbourne, despite clawing his way back from two sets down.
He was in the Scot's section of the draw, and the pair were on course for a quarter-final meeting.
"I would say [Del Potro's defeat] was a surprise," said Murray.
"He was the favourite for the match, but often there's surprises in Australia, at this event. It's the first tournament he's played this year."
Chardy will now play Andreas Seppi for a place in the last eight.